C-cell hyperplasia

C-cell hyperplasia Medullary thyroid carcinoma Nonthyroidal cancers... 

FIGURE 10.20 C-cell hyperplasia from a patient with multiple endocrine neoplasia 2A. This immunoperoxidase stain for calcitonin is strongly positive in the C cells, whereas the follicular cells are negative. 

C cells in normal glands have an exclusive intrafollicular topography and are concentrated at the junctions of the upper and middle thirds of the lobes (Fig. 10.19). In patients with multiple endocrine neoplasia, type 2 (MEN2), C-cell hyperplasia has been recognized as the precursor of medullary thyroid carcinoma. Detailed immunohistochemical studies have shown that C-cell hyperplasia is characterized by increased numbers of C cells within the follicles in the same regions of the gland where C cells normally predominate (Fig. 10.20). These relationships are maintained in areas of more advanced C-cell hyperplasia, where C cells often completely encircle and displace the follicular epithelium centrally. Nodular hyperplasia is characterized by the complete obliteration... 

Familial forms of medullary carcinoma are preceded in their development by C-cell hyperplasia. 

Komminoth P, Roth J, Saremaslani P, et al. Polysialic acid of the neural cell adhesion molecule in the human thyroid A marker for medullary thyroid carcinoma and primary C-cell hyperplasia An immunohistochemical study on 79 thyroid lesions. Am Surg Pathol. 1994 18 399-411. 

Perry A, Molberg K, Albores-Saavedra J. Physiologic versus neoplastic C-cell hyperplasia of the thyroid Separation of distinct histologic and biologic entities. Cancer. 1996 77 750-756. 

REGULATION OF SECRETION Calcitonin secretion increases with hypercalcemia and decreases when plasma Ca " is low the hormone in circulation has a t of 10 minutes. Circulating concentrations are normally low (<15 pg/mL in males and 10 pg/mL in females) but can be markedly elevated with C cell hyperplasia or medullary thyroid cancer. 

Tumorigenidty The FDA adverse events database has been used to examine the association of exenatide with cancer [39 "]. Pancreatic cancer, thyroid cancer, and all cancers were predefined events. In an attempt to limit reporting bias, the events rates were compared with other hypoglycemic drugs, and control events that were not thought to be increased by exenatide were reviewed. There was a 2.9-fold increase in pancreatic cancer in those who used exenatide compared with other therapies. Thyroid cancer occurred 4.7 times more often. There was no increase in the reporting of other cancers. GLP-1 receptors are expressed in the pancreas. Thyroid tumors have been reported in mice treated with liraglutide, and GLP-1 therapy causes C-cell hyperplasia in rats. 

In the Wistar rat, the proportion of C-cells to follicular cells was 4.5 % on the day of birth and increased progressively to 10.4 % by 120 days (MartIn-Lacave et al. 1992). The highest density of C-cells was noted in the mid-region of the lobes along a longitudinal axis. From 3 to 24 months of life, 27.5 % of female rats showed a normal C-cell pattern, 55.0% showed C-cell hyperplasia and 17.5 % showed C-cell tumours while 57.5 % of male rats showed a normal C-cell pattern, 32.5 % showed C-cell hyperplasia, and 10 % showed C-cell tumours (MartIn-Lacave etal. 1999). 

In the Sprague-Dawley rat, areas of C-cell hyperplasia appeared with age (Rao-Rupanagudi et al. 1992). 

Monitoring Therapy A high-dose calcium test may be used as a potent biomarker for the diagnosis and follow-up of medullary thyroid cancer (MTC), since it is well tolerated and is cost effective compared to the pentagastrin test. A recent study identified that the best levels of basal calcitonin (bCT) to distinguish normal and C-cell hyperplasia (CCH) cases, from MTC patients were above 18.7pg/ml in females and above 68pg/ml in males while calcium-stimulated calcitonin levels above 184 pg/ml in females and above 1620pg/ml in males were most accurate to separate normal and CCH cases from patients with MTC [74 ]. 

T3. Tlirbat-Herrera, E. A., Hancock, C., Cabello-Inchausti, B., and Herrera, G. A., Plasma cell hyperplasia and monoclonal paraproteinemia in AIDS. Arch. Pathol. Lab. Med. 17(5), 497-501 (1993). 

Dunlop, S.P., Jenkins, D., Neal, K.R., and Spiller, R.C. 2003. Relative importance of enterochro-maffin cell hyperplasia, anxiety, and depression in postinfectious IBS. Gastroenterology 125 1651-1659. 

Poirier, H., Rouault, C., Clement, L., Niot, I., Monnot, M. C., Guerre-Millo, M., and Besnard, P. 2005. Hyperinsulinaemia triggered by dietary conjugated linoleic acid is associated with a decrease in leptin and adiponectin plasma levels and pancreatic beta cell hyperplasia in the mouse. Diabetologia, 48,1059-1065. 

Clegg, E.D., J.C. Cook, R.E. Chapin, P.M. Foster, and G.P. Daston. 1997. Leydig cell hyperplasia and adenoma formation Mechanisms and relevance to humans. Reprod. Toxicol. 11 (1) 107-121. 

The proposed origin of tumors with mixed medullary and follicular features has been controversial. Volante and coworkers have proposed an origin from two different progenitors. According to their hypothesis, neoplastic transformation of C cells leads to the development of medullary thyroid carcinoma with entrapped normal follicles. Stimulation of the entrapped follicular cells results in hyperplasia and ultimately follicular (or papillary) neoplasia (hostage hypothesis). Neoplastic C cells and follicular cells would have the capacity to metastasize and could explain the presence of both components in distant sites. 

Calcitonin is secreted continuously under conditions of normocalcemia, and the synthesis of calcitonin is increased when the calcium concentrations in plasma and intracellular fluids increase. Hypermagnesemia has a similar effect on calcitonin production. In hypocalcemia, the production of calcitonin falls. The gastrointestinal hormones—gastrin, glucagon, cholecystokinin, and secretin—and high dietary calcium also stimulate calcitonin production. Long-term hypercalcemia may cause hyperplasia of the C cells. 

Hooth, M.J., DeAngelo, A.B., George, M.H., Gaillard, E.T., Travlos, G.S., Boorman, G.A. Wolf, D.C. (2001) Subohronic sodium chlorate exposure in drinking water results in a ooncentration-dependent increase in rat thyroid follicular cell hyperplasia. Toxicol. Pathol. 29(2), 250-259,... 

The infusion of calcitonin to rats induces increased calcium deposition in the bone and hypocalcemia. Thus, the hormone has properties antagonistic to those of parathormone. Fluorescent antibody techniques have demonstrated that the hormone is secreted by the C cells of the thyroid gland. A light cell hyperplasia outside the follicular walls of the thyroid has been observed in mice with hereditary hypocalcemia. 

Harleman JH, Betton GR, Dormer C, McCrossan M (1987) Gastric neuroendocrine cell hyperplasia after treatment with the long-acting, potent H2-receptor antagonist SK F 93479. Scand J Gastroenterol 22 595-600... 

G. R. Lankas and C. P. Peter, Induction of reversible urothelial cell hyperplasia in rats by clorsulon, a flukicide with weak carbonic anhydrase inhibitory activity. Food Chem. Toxicol., 1992, 30, 297-306. 

K. C. (2005) Titanium dioxide particle-induced goblet cell hyperplasia association with mast cells and IL-13. Respiratory Research, 13(6), 34. 

In animal studies, mirex (a nonmutagenic hepatocarcinogen) promoted mouse skin squamous carcinomas and papillomas after initiation with 7,12-dimethyl-benz[a]anthracene (DMBA) for 1 week. Mirex, also, potentiated the promotional potency of the phorbol ester tumor promoter, 12-0 -tetradecanoylphorbol-13-acetate (TPA). There was a 90% incidence (activation) of the c-Ha-ras tumor gene in these co-promoted tumors. When both mirex and TPA gave a similar tumor yield, only the TPA response was associated with biochemical markers of enhanced cell proliferation, induction of epidermal ornithine decarboxylase activity and increased DNA synthesis, and hyperplasia. Thus, there is evidence for a dual effect of mirex during co-promotion first, as an independent tumor promoter with a mechanism different than that of phorbol esters and second, as a compound that also potentiates skin tumor promotion by TPA (Meyer et al. 1993, 1994 Moser et al. 1992, 1993). 

Wood, B. L., Bacchi, M. M., Bacchi, C. E., Kidd, P., and Gown, A. M. (1994) Immunocytochemical differentiation of reactive hyperplasia from follicular lymphoma using monoclonal antibodies to cell surface and proliferation-related markers. Appl. Immunohistochem. 2,48-53. 

Murphy, M. A., R. G. Schnall, D. J. Venter, L. Barnett, I. Bertoncello, C. B. Thien, W. Y. Langdon, and D. D. Bowtell. Tissue hyperplasia arul enhanced T-cell signalling via ZAP-70 in c-Cbl-deficient mice. Mol Cell Biol. 18 4872-4882.1998. 

Fero, M., Rivkin, M., Tasch, M., Porter, P., Carow, C., Fiipo, E., Tsai, L., Broudy, V., Perlmutter, R., Kaushansky, K., and Roberts, J. (1996). A syndrome of multi-organ hyperplasia with features of gigantism, tumorigenesis and female sterility in p27 -deficient mice. Cell 85,733-744. 

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